1. Field of Invention
This invention relates to novel 4-substituted piperidinecarboxylic acid esters which inhibit the absorption of cholesterol in rats and have been shown to inhibit the enzymes cholesterol ester hydrolase (CEH) and/or acyl coenzyme A: cholesterol acyltransferase (ACAT). Each of these enzymes is implicated in the reesterification and absorption of exogenous cholesterol. It has been shown that the removal of CEH from pancreatic juice results in an 80% reduction in the uptake of cholesterol (Gallo et al, Journal of Lipid Research 25, 604-612 (1984)). Reduction of high blood cholesterol levels is a concern of health conscious individuals. The association between high serum cholesterol levels and coronary heart disease is well documented, and consequently, compounds of this invention may be useful in the treatment of atherosclerosis, familial hypercholesterolemia, hyperlipemia, and like diseases.
2. Information Disclosure Statement
Hoisie, et al., J. Biol. Chem. 262, 260-264 (1987) has reported that p-nitrophenyl-N-alkylcarbamates and cholesteryl-N-alkylcarbamates inhibit the porcine pancreatic cholesterol esterase (CEH) hydrolysis of p-nitrophenylbutyrate, thus an indication that phenylcarbamates may have utility in decreasing blood cholesterol via inhibition of CEH and/or ACAT. Cholesterol ester hydrolase inhibition by 4-phenoxyphenyl esters of N-alkylcarbamic acids which includes the intermediate 4-phenoxyphenyl esters of 4-hydroxy-1-piperidinecarboxylic acid used as intermediates in the present invention is disclosed in our commonly owned U.S. Application Ser. No. 07/594,241 filed Oct. 9, 1990.